Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN

Level of systolic blood pressure within the normal range and risk of recurrent stroke.

JAMA. 2011 Nov 16;306(19):2137-44

Authors: Ovbiagele B, Diener HC, Yusuf S, Martin RH, Cotton D, Vinisko R, Donnan GA, Bath PM,

Abstract
CONTEXT: Recurrent stroke prevention guidelines suggest that larger reductions in systolic blood pressure (SBP) are positively associated with a greater reduction in the risk of recurrent stroke and define an SBP level of less than 120 mm Hg as normal. However, the association of SBP maintained at such levels with risk of vascular events after a recent ischemic stroke is unclear.
OBJECTIVE: To assess the association of maintaining low-normal vs high-normal SBP levels with risk of recurrent stroke.
DESIGN, SETTING, AND PATIENTS: Post hoc observational analysis of a multicenter trial involving 20,330 patients (age ≥50 years) with recent non-cardioembolic ischemic stroke; patients were recruited from 695 centers in 35 countries from September 2003 through July 2006 and followed up for 2.5 years (follow-up ended on February 8, 2008). Patients were categorized based on their mean SBP level: very low-normal (<120 mm Hg), low-normal (120-<130 mm Hg), high-normal (130-<140 mm Hg), high (140-<150 mm Hg), and very high (≥150 mm Hg).
MAIN OUTCOME MEASURES: The primary outcome was first recurrence of stroke of any type and the secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes.
RESULTS: The recurrent stroke rates were 8.0% (95% CI, 6.8%-9.2%) for the very low-normal SBP level group, 7.2% (95% CI, 6.4%-8.0%) for the low-normal SBP group, 6.8% (95% CI, 6.1%-7.4%) for the high-normal SBP group, 8.7% (95% CI, 7.9%-9.5%) for the high SBP group, and 14.1% (95% CI, 13.0%-15.2%) for the very high SBP group. Compared with patients in the high-normal SBP group, the risk of the primary outcome was higher for patients in the very low-normal SBP group (adjusted hazard ratio [AHR], 1.29; 95% CI, 1.07-1.56), in the high SBP group (AHR, 1.23; 95% CI, 1.07-1.41), and in the very high SBP group (AHR, 2.08; 95% CI, 1.83-2.37). Compared with patients in the high-normal SBP group, the risk of secondary outcome was higher for patients in the very low-normal SBP group (AHR, 1.31; 95% CI, 1.13-1.52), in the low-normal SBP group (AHR, 1.16; 95% CI, 1.03-1.31), in the high SBP group (AHR, 1.24; 95% CI, 1.11-1.39), and in the very high SBP group (AHR, 1.94; 95% CI, 1.74-2.16).
CONCLUSION: Among patients with recent non-cardioembolic ischemic stroke, SBP levels during follow-up in the very low-normal (<120 mm Hg), high (140-<150 mm Hg), or very high (≥150 mm Hg) range were associated with increased risk of recurrent stroke.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00153062.

PMID: 22089721 [PubMed - indexed for MEDLINE]

Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis.

JAMA. 2011 Nov 23;306(20):2248-54

Authors: Walkey AJ, Wiener RS, Ghobrial JM, Curtis LH, Benjamin EJ

Abstract
CONTEXT: New-onset atrial fibrillation (AF) has been reported in 6% to 20% of patients with severe sepsis. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in the setting of severe sepsis is uncertain.
OBJECTIVE: To determine the in-hospital stroke and in-hospital mortality risks associated with new-onset AF in patients with severe sepsis.
DESIGN AND SETTING: Retrospective population-based cohort of California State Inpatient Database administrative claims data from nonfederal acute care hospitals for January 1 through December 31, 2007.
PATIENTS: Data were available for 3,144,787 hospitalized adults. Severe sepsis (n = 49,082 [1.56%]) was defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 995.92. New-onset AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission.
MAIN OUTCOME MEASURES: A priori outcome measures were in-hospital ischemic stroke (ICD-9-CM codes 433, 434, or 436) and mortality.
RESULTS: Patients with severe sepsis were a mean age of 69 (SD, 16) years and 48% were women. New-onset AF occurred in 5.9% of patients with severe sepsis vs 0.65% of patients without severe sepsis (multivariable-adjusted odds ratio [OR], 6.82; 95% CI, 6.54-7.11; P < .001). Severe sepsis was present in 14% of all new-onset AF in hospitalized adults. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital stroke (75/2896 [2.6%] vs 306/46,186 [0.6%] strokes; adjusted OR, 2.70; 95% CI, 2.05-3.57; P < .001) and in-hospital mortality (1629 [56%] vs 18,027 [39%] deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P < .001). Findings were robust across 2 definitions of severe sepsis, multiple methods of addressing confounding, and multiple sensitivity analyses.
CONCLUSION: Among patients with severe sepsis, patients with new-onset AF were at increased risk of in-hospital stroke and death compared with patients with no AF and patients with preexisting AF.

PMID: 22081378 [PubMed - indexed for MEDLINE]

Treatment of brain arteriovenous malformations: a systematic review and meta-analysis.

JAMA. 2011 Nov 9;306(18):2011-9

Authors: van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ

Abstract
CONTEXT: Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies.
OBJECTIVES: To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes.
DATA SOURCES: We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011.
STUDY SELECTION AND DATA EXTRACTION: We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration.
DATA SYNTHESIS: We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization.
CONCLUSIONS: Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified.

PMID: 22068993 [PubMed - indexed for MEDLINE]

Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial.

JAMA. 2011 Nov 9;306(18):1983-92

Authors: Powers WJ, Clarke WR, Grubb RL, Videen TO, Adams HP, Derdeyn CP,

Abstract
CONTEXT: Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically.
OBJECTIVE: To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia.
DESIGN: Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010.
SETTING: Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers.
PARTICIPANTS: Patients with arteriographically confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Of 195 patients who were randomized, 97 were randomized to receive surgery and 98 to no surgery. Follow-up for the primary end point until occurrence, 2 years, or termination of trial was 99% complete. No participant withdrew because of adverse events.
INTERVENTIONS: Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Antithrombotic therapy and risk factor intervention were recommended for all participants.
MAIN OUTCOME MEASURE: For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days after surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery, the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within 2 years of randomization.
RESULTS: The trial was terminated early for futility. Two-year rates for the primary end point were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (P = .78, Z test), a difference of 1.7% (95% CI, -10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.4% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group, a difference of 12.4% (95% CI, 4.9% to 19.9%).
CONCLUSION: Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared with medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00029146.

PMID: 22068990 [PubMed - indexed for MEDLINE]

Care and outcomes in patients with ischemic stroke with and without preexisting dementia.

Neurology. 2011 Nov 1;77(18):1664-73

Authors: Saposnik G, Cote R, Rochon PA, Mamdani M, Liu Y, Raptis S, Kapral MK, Black SE, ,

Abstract
OBJECTIVE: To describe clinical characteristics and evaluate processes of care and outcomes at discharge in patients with ischemic stroke with and without preexisting dementia.
METHODS: Retrospective cohort study using the Registry of the Canadian Stroke Network including patients presenting with an acute ischemic stroke between 2003 and 2008. Preexisting dementia was defined as any type of dementia that was present prior to the index stroke case. Palliative patients were excluded. Demographic information, clinical presentation, selected process measures (e.g., thrombolysis, admission to stroke unit, carotid imaging, stroke prevention), pneumonia, death, disability, and disposition at discharge were analyzed.
RESULTS: Among 9,304 eligible patients with an acute ischemic stroke, 702 (9.1%) had a history of dementia. Patients with dementia were older (mean age 81 vs 70 years; p < 0.001), had more severe strokes (Canadian Neurological Scale score <4, 20.7% vs 10.5%; p < 0.001), and were more likely to have atrial fibrillation (22.8% vs 15.3%; p < 0.001) than those without dementia. Patients with dementia were slightly less likely to be admitted to a stroke unit (63% vs 67.6%; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96) or to receive thrombolysis (10.5% vs 15.7%; OR 0.63, 95% CI 0.49-0.81). There were no differences in other performance measures. Patients with preexisting dementia had higher disability at discharge (OR 3.20, 95% CI 2.64-3.87) and were less likely to be discharged to their prestroke place of residence (24% vs 45%; p < 0.001).
CONCLUSIONS: In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system.

PMID: 22042795 [PubMed - indexed for MEDLINE]

Long-term outcome poststroke: predictors of activity limitation and participation restriction.

Arch Phys Med Rehabil. 2011 Nov;92(11):1802-8

Authors: Gadidi V, Katz-Leurer M, Carmeli E, Bornstein NM

Abstract
OBJECTIVES: To describe long-term activity limitation, participation restriction, and patients' overall perception of recovery among stroke patients 4 years poststroke, and to evaluate the association between the factors. In addition, the study investigated those factors present at the time of stroke onset, which could predict the level of activity limitation and participation restriction at 4 years poststroke.
DESIGN: Prospective, 4-year follow-up study.
SETTING: Subjects' homes, via telephone.
PARTICIPANTS: All first ever stroke patients (N=139) admitted to the Sheba Medical Center in Israel between February and March 2004 were followed and reassessed for activity and participation restrictions.
INTERVENTIONS: Not applicable.
MAIN OUTCOME MEASURES: Barthel index (BI) (activity limitation, BI<95) and Frenchay Activities Index (FAI) (participation restriction, FAI<30). Perception of recovery was assessed by 2 simple questions.
RESULTS: At 4 years poststroke, 9 patients (6.4%) were lost to follow-up, 71 (54.1%) patients had survived; 42.3% with activity limitation, 28.2% were classified as restricted in participation, and 78.1% felt they had not completely recovered. Age at stroke onset and disability in the acute phase were the most significant predictors of activity limitation at 4 years poststroke. None of the demographic characteristics or baseline clinical features predicted participation restriction. A positive association (ρ=0.6) was noted between activity limitation and participation restriction 4 years poststroke.
CONCLUSIONS: This is the first study to describe long-term outcomes poststroke in Israel. Activity limitation and participation restriction remain highly prevalent up to 4 years after stroke. The potential influence of additional factors (psychosocial, cognitive, and environmental) as predictors of participation restriction should be topics for future investigation.

PMID: 22032214 [PubMed - indexed for MEDLINE]

Health-related quality of life after stroke: does response shift occur in self-perceived physical function?

Arch Phys Med Rehabil. 2011 Nov;92(11):1762-9

Authors: Barclay-Goddard R, Lix LM, Tate R, Weinberg L, Mayo NE

Abstract
OBJECTIVE: To determine whether response shift (a change in the self-perceived meaning of health-related quality of life [HRQL]) was present in a model of physical function over time poststroke.
DESIGN: Secondary data analysis of a longitudinal observational study.
SETTING: Community.
PARTICIPANTS: A consecutive sample of stroke survivors (N=677) at 1, 3, 6, and 12 months poststroke was included. Sixty-seven individuals were approached, but refused. Sixty-seven percent completed the study at 12 months. Mean age was 68 years; 45% of the participants were women.
INTERVENTIONS: Not applicable.
MAIN OUTCOMES MEASURES: The Medical Outcomes Study 36-Item Short-Form Health Survey, Euroqol, Stroke Impact Scale, Preference-Based Stroke Index, and the Health Utilities Index.
RESULTS: Structural equation modeling was used to identify response shift. A chi-square difference test between constrained and unconstrained longitudinal models suggested the presence of response shift in the data. Reprioritization response shift, a change in relative importance of domains, was observed for physical activites. Recalibration response shift, a change in internal standards of measurement, was observed in physical activities, stairs, walking, and hand function.
CONCLUSIONS: Response shift has implications for the measurement of change in physical function. Measures that focus on difficulty in task performance may be sensitive to response shift, resulting in a change in perceived HRQL over time. This has implications for choosing self-perceived or performance-based measures to detect change in physical function.

PMID: 22032211 [PubMed - indexed for MEDLINE]

Ultraearly hematoma growth predicts poor outcome after acute intracerebral hemorrhage.

Neurology. 2011 Oct 25;77(17):1599-604

Authors: Rodriguez-Luna D, Rubiera M, Ribo M, Coscojuela P, Piñeiro S, Pagola J, Hernandez-Guillamon M, Ibarra B, Romero F, Alvarez-Sabin J, Montaner J, Molina CA

Abstract
OBJECTIVE: To investigate the impact of the adjustment of initial intracerebral hemorrhage (ICH) volume by onset-to-imaging time (ultraearly hematoma growth [uHG]) on further hematoma enlargement and outcome in patients with acute ICH.
METHODS: We studied 133 patients with acute (<6 hours) supratentorial ICH. Patients underwent baseline and 24-hour CT scans for ICH volume measurement, and a CT angiography (CTA) for the detection of the spot sign. We defined uHG as the relation between baseline ICH volume/onset-to-imaging time, hematoma growth (HG) as hematoma enlargement >33% or >6 mL at 24 hours, early neurologic deterioration (END) as increase ≥4 points in the NIH Stroke Scale score or death at 24 hours, and poor long-term outcome as modified Rankin Scale score >2 at 3 months.
RESULTS: The uHG was significantly faster in spot sign patients (p < 0.001), as well as in patients who experienced HG (p = 0.021), END (p < 0.001), 3-month mortality (p < 0.001), and poor long-term outcome (p < 0.001). The uHG improved the accuracy of baseline ICH volume in the prediction of END (sensitivity 93.1% vs 82.8%, specificity 85.3% vs 82.4%) and 3-month mortality (sensitivity 77.5% vs 70%, specificity 87.9% vs 84.6%). A uHG >10.2 mL/hour emerged as the most powerful predictor of HG (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.39-9.07, p = 0.008), END (OR 70.22, 95% CI 14.63-337.03, p < 0.001), 3-month mortality (OR 16.96, 95% CI 5.32-54.03, p < 0.001), and poor long-term outcome (OR 6.19, 95% CI 1.32-28.98, p = 0.021).
CONCLUSIONS: The uHG represents a powerful and easy-to-use tool for improving the prediction of HG and outcome in patients with acute ICH.

PMID: 21998314 [PubMed - indexed for MEDLINE]

Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial.

Lancet. 2011 Nov 12;378(9804):1699-706

Authors: Middleton S, McElduff P, Ward J, Grimshaw JM, Dale S, D'Este C, Drury P, Griffiths R, Cheung NW, Quinn C, Evans M, Cadilhac D, Levi C,

Abstract
BACKGROUND: We assessed patient outcomes 90 days after hospital admission for stroke following a multidisciplinary intervention targeting evidence-based management of fever, hyperglycaemia, and swallowing dysfunction in acute stroke units (ASUs).
METHODS: In the Quality in Acute Stroke Care (QASC) study, a single-blind cluster randomised controlled trial, we randomised ASUs (clusters) in New South Wales, Australia, with immediate access to CT and on-site high dependency units, to intervention or control group. Patients were eligible if they spoke English, were aged 18 years or older, had had an ischaemic stroke or intracerebral haemorrhage, and presented within 48 h of onset of symptoms. Intervention ASUs received treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction with multidisciplinary team building workshops to address implementation barriers. Control ASUs received only an abridged version of existing guidelines. We recruited pre-intervention and post-intervention patient cohorts to compare 90-day death or dependency (modified Rankin scale [mRS] ≥2), functional dependency (Barthel index), and SF-36 physical and mental component summary scores. Research assistants, the statistician, and patients were masked to trial groups. All analyses were done by intention to treat. This trial is registered at the Australia New Zealand Clinical Trial Registry (ANZCTR), number ACTRN12608000563369.
FINDINGS: 19 ASUs were randomly assigned to intervention (n=10) or control (n=9). Of 6564 assessed for eligibility, 1696 patients' data were obtained (687 pre-intervention; 1009 post-intervention). Results showed that, irrespective of stroke severity, intervention ASU patients were significantly less likely to be dead or dependent (mRS ≥2) at 90 days than control ASU patients (236 [42%] of 558 patients in the intervention group vs 259 [58%] of 449 in the control group, p=0·002; number needed to treat 6·4; adjusted absolute difference 15·7% [95% CI 5·8-25·4]). They also had a better SF-36 mean physical component summary score (45·6 [SD 10·2] in the intervention group vs 42·5 [10·5] in the control group, p=0·002; adjusted absolute difference 3·4 [95% CI 1·2-5·5]) but no improvement was recorded in mortality (21 [4%] of 558 in intervention group and 24 [5%] of 451 in the control group, p=0·36), SF-36 mean mental component summary score (49·5 [10·9] in the intervention group vs 49·4 [10·6] in the control group, p=0·69) or functional dependency (Barthel Index ≥60: 487 [92%] of 532 patients vs 380 [90%] of 423 patients; p=0·44).
INTERPRETATION: Implementation of multidisciplinary supported evidence-based protocols initiated by nurses for the management of fever, hyperglycaemia, and swallowing dysfunction delivers better patient outcomes after discharge from stroke units. Our findings show the possibility to augment stroke unit care.
FUNDING: National Health & Medical Research Council ID 353803, St Vincent's Clinic Foundation, the Curran Foundation, Australian Diabetes Society-Servier, the College of Nursing, and Australian Catholic University.

PMID: 21996470 [PubMed - indexed for MEDLINE]

Change in high-density lipoprotein cholesterol and risk of subsequent hospitalization for coronary artery disease or stroke among patients with type 2 diabetes mellitus.

Am J Cardiol. 2011 Oct 15;108(8):1124-8

Authors: Nichols GA, Vupputuri S, Rosales AG

Abstract
The association between the changes in high-density lipoprotein (HDL) cholesterol and the risk of cardiovascular (CVD) or cerebrovascular hospitalization among patients with type 2 diabetes remains unclear. We conducted a retrospective observational cohort study of 30,067 members of the Kaiser Permanente Northwest and Georgia regions, who had type 2 diabetes and 2 HDL cholesterol measurements 6 to 24 months apart in 2001 to 2006. We followed up the cohort for ≤8 years (through 2009) to determine whether the change in HDL cholesterol was associated with subsequent CVD hospitalization. We examined the HDL cholesterol change continuously and by 3 categories: HDL cholesterol increased ≥6.5 mg/dl, decreased ≥6.5 mg/dl, or remained within ±6.4 mg/dl. The Cox regression models were adjusted for the baseline HDL cholesterol and demographic and clinical risk factors. During a mean follow-up of 55.8 ± 23.8 months, 3,023 patients (10.1%) experienced a CVD hospitalization. After multivariate adjustment, each 5 mg/dl of baseline HDL cholesterol was significantly associated with a 6% lower CVD hospitalization risk (hazard ratio 0.94 per 5 mg/dl, 95% confidence interval 0.92 to 0.95, p <0.0001) and each 5-mg/dl increase in HDL cholesterol was associated with a 4% CVD risk reduction (hazard ratio 0.96, 95% confidence interval 0.94 to 0.99, p <0.003). In the categorical analysis, a ≥6.5-mg/dl HDL cholesterol decrease was associated with an 11% increased CVD risk (hazard ratio 1.11, 95% confidence interval 1.00 to 1.24, p = 0.047) and a ≥6.5-mg/dl increase was associated with an 8% CVD risk reduction (hazard ratio 0.92, 95% confidence interval 0.84 to 1.01, p = 0.077) relative to those with stable HDL cholesterol. In conclusion, our results add to the growing body of evidence that increasing the HDL cholesterol levels might be an important strategy for CVD risk reduction. The prevention of HDL cholesterol decreases could be equally important.

PMID: 21985949 [PubMed - indexed for MEDLINE]

Adherence to the Mediterranean diet in relation to acute coronary syndrome or stroke nonfatal events: a comparative analysis of a case/case-control study.

Am Heart J. 2011 Oct;162(4):717-24

Authors: Kastorini CM, Milionis HJ, Ioannidi A, Kalantzi K, Nikolaou V, Vemmos KN, Goudevenos JA, Panagiotakos DB

Abstract
BACKGROUND: Although the role of Mediterranean diet on cardiovascular disease prevention has long been evaluated and understood, its association with the development of stroke has been rarely examined. The aim of the present work was to comparatively evaluate the association between adherence to the Mediterranean diet and the development of an acute coronary syndrome (ACS) or ischemic stroke.
METHODS: During the period from 2009 to 2010, 1,000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke, and 500 population-based, control subjects, 1-for-1 matched to the patients by age and sex. Sociodemographic, clinical, psychological, dietary, and other lifestyle characteristics were measured. Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range 0-55).
RESULTS: After various adjustments were made, it was observed that for each 1-of-55-unit increase of the MedDietScore, the corresponding odds ratio for having an ACS was 0.91 (95% CI 0.87-0.96), whereas regarding stroke, it was 0.88 (95% CI 0.82-0.94).
CONCLUSIONS: The present work extended the current knowledge about the cardioprotective benefits from the adoption of the Mediterranean diet by showing an additional protective effect on ischemic stroke development.

PMID: 21982665 [PubMed - indexed for MEDLINE]

Improvement in use of anticoagulation therapy in patients with ischemic stroke: results from Get With The Guidelines-Stroke.

Am Heart J. 2011 Oct;162(4):692-699.e2

Authors: Lewis WR, Fonarow GC, Grau-Sepulveda MV, Smith EE, Bhatt DL, Hernandez AF, Olson D, Peterson ED, Schwamm LH

Abstract
BACKGROUND: Anticoagulation therapy reduces thromboembolic events in patients with atrial fibrillation (AF) and has a class I indication for ischemic stroke patients with AF and no contraindications. We determined the patient and hospital level characteristics associated with an increased use of anticoagulation, including participation in the Get With The Guidelines-Stroke (GWTG-Stroke) Program.
METHODS: We assessed the use of anticoagulation at hospital discharge in eligible AF patients with stroke or transient ischemic attack (TIA) at 1,354 participating hospitals between April 1, 2003, and April 1, 2010.
RESULTS: Patients with AF (n = 197,778) represented 20.5% of patients with ischemic stroke/TIA. Among patients with AF, 47.6% (n = 94,119) were deemed eligible for anticoagulation, and of these, 94.0% were discharged on therapy. Older patients, African American or Hispanic patients, and those with diabetes were less likely to receive anticoagulation. Hospitals with a higher volume of patients with stroke were more likely to treat with anticoagulation. The Joint Commission Primary Stroke Centers were also more likely to treat eligible patients (odds ratio 2.16, 95% CI 1.82-2.56, P < .0001). From 2003 to 2010, contraindications to anticoagulation therapy declined from 69.7% to 28.4% (P < .0001 for trend). Anticoagulation among eligible patients improved from 88.4% to 95.2% (P < .0001) for 7 years of participation. Time in GWTG-Stroke was associated with improved anticoagulation use (adjusted odds ratio per year in program, 1.11, 95% CI 1.06-1.16, P < .001).
CONCLUSIONS: Use of anticoagulation among stroke patients with AF has increased to very high levels overall in GWTG-Stroke over time. Future efforts should focus on improving use among selected populations.

PMID: 21982662 [PubMed - indexed for MEDLINE]

Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS).

Am Heart J. 2011 Oct;162(4):597-605

Authors: Ridker PM, Thuren T, Zalewski A, Libby P

Abstract
BACKGROUND: Inflammation contributes to all phases of the atherothrombotic process, and patients with elevated inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP) have increased vascular risk. Yet, it remains unknown whether direct inhibition of inflammation will reduce cardiovascular event rates.
DESIGN: The CANTOS will evaluate whether interleukin-1β (IL-1β) inhibition as compared with placebo can reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable patients with coronary artery disease who remain at high vascular risk due to persistent elevations of hsCRP (>2 mg/L) despite contemporary secondary prevention strategies. Canakinumab is a human monoclonal antibody that selectively neutralizes IL-1β, a proinflammatory cytokine that plays multiple roles in the atherothrombotic process and that undergoes activation by the nucleotide-binding leucine-rich repeat-containing pyrin receptor 3 inflammasome, a process promoted by cholesterol crystals. Canakinumab significantly reduces systemic C-reactive protein and other inflammatory biomarker levels, is generally well tolerated, and is currently indicated for the treatment of inherited IL-1β driven inflammatory diseases such as the Muckle-Wells syndrome. In a multinational collaborative effort using an event-driven intention-to-treat protocol, CANTOS will randomly allocate 17,200 stable postmyocardial infarction patients with persistent elevation of hsCRP to either placebo or to canakinumab at doses of 50, 150, or 300 mg every 3 months, administered subcutaneously. All participants will be followed up over an estimated period of up to 4 years for the trial primary end point (nonfatal myocardial infarction, nonfatal stroke, cardiovascular death) as well as for other vascular events, total mortality, adverse events, and specific clinical end points associated with inflammation including new onset diabetes, venous thrombosis, and atrial fibrillation.
SUMMARY: If positive, CANTOS would confirm the inflammatory hypothesis of atherothrombosis and provide a novel cytokine-based therapy for the secondary prevention of cardiovascular disease and new-onset diabetes.

PMID: 21982649 [PubMed - indexed for MEDLINE]

The neural correlates of inner speech defined by voxel-based lesion-symptom mapping.

Brain. 2011 Oct;134(Pt 10):3071-82

Authors: Geva S, Jones PS, Crinion JT, Price CJ, Baron JC, Warburton EA

Abstract
The neural correlates of inner speech have been investigated previously using functional imaging. However, methodological and other limitations have so far precluded a clear description of the neural anatomy of inner speech and its relation to overt speech. Specifically, studies that examine only inner speech often fail to control for subjects' behaviour in the scanner and therefore cannot determine the relation between inner and overt speech. Functional imaging studies comparing inner and overt speech have not produced replicable results and some have similar methodological caveats as studies looking only at inner speech. Lesion analysis can avoid the methodological pitfalls associated with using inner and overt speech in functional imaging studies, while at the same time providing important data about the neural correlates essential for the specific function. Despite its advantages, a study of the neural correlates of inner speech using lesion analysis has not been carried out before. In this study, 17 patients with chronic post-stroke aphasia performed inner speech tasks (rhyme and homophone judgements), and overt speech tasks (reading aloud). The relationship between brain structure and language ability was studied using voxel-based lesion-symptom mapping. This showed that inner speech abilities were affected by lesions to the left pars opercularis in the inferior frontal gyrus and to the white matter adjacent to the left supramarginal gyrus, over and above overt speech production and working memory. These results suggest that inner speech cannot be assumed to be simply overt speech without a motor component. It also suggests that the use of overt speech to understand inner speech and vice versa might result in misleading conclusions, both in imaging studies and clinical practice.

PMID: 21975590 [PubMed - indexed for MEDLINE]

Transcobalamin 2 variant associated with poststroke homocysteine modifies recurrent stroke risk.

Neurology. 2011 Oct 18;77(16):1543-50

Authors: Hsu FC, Sides EG, Mychaleckyj JC, Worrall BB, Elias GA, Liu Y, Chen WM, Coull BM, Toole JF, Rich SS, Furie KL, Sale MM

Abstract
OBJECTIVES: The Vitamin Intervention for Stroke Prevention trial found an association between baseline poststroke homocysteine (Hcy) and recurrent stroke. We investigated genes for enzymes and cofactors in the Hcy metabolic pathway for association with Hcy and determined whether associated single nucleotide polymorphisms (SNPs) influenced recurrent stroke risk.
METHODS: Eighty-six SNPs in 9 candidate genes (BHMT1, BHMT2, CBS, CTH, MTHFR, MTR, MTRR, TCN1, and TCN2) were genotyped in 2,206 subjects (83% European American). Associations with Hcy measures were assessed using linear regression models assuming an additive genetic model, adjusting for age, sex, and race and additionally for baseline Hcy when postmethionine load change was assessed. Associations with recurrent stroke were evaluated using survival analyses.
RESULTS: Five SNPs in the transcobalamin 2 (TCN2) gene were associated with baseline Hcy (false discovery rate [FDR]-adjusted p = 0.049). TCN2 SNP rs731991 was associated with recurrent stroke risk in the low-dose arm of the trial under a recessive model (log-rank test p = 0.009, hazard ratio 0.34). Associations with change in postmethionine load Hcy levels were found with 5 SNPs in the cystathionine β-synthase (CBS) gene (FDR-adjusted p < 0.031).
CONCLUSIONS: TCN2 variants contribute to poststroke Hcy levels, whereas variants in the CBS gene influence Hcy metabolism. Variation in the TCN2 gene also affects recurrent stroke risk in response to cofactor therapy.

PMID: 21975197 [PubMed - indexed for MEDLINE]

Effects of intensive arm training with an electromechanical orthosis in chronic stroke patients: a preliminary study.

Arch Phys Med Rehabil. 2011 Nov;92(11):1746-53

Authors: de Araújo RC, Junior FL, Rocha DN, Sono TS, Pinotti M

Abstract
OBJECTIVES: To evaluate the use of an electromechanical device, comprising an exoskeleton, a static orthosis, and a glove, for functional rehabilitation of the elbow and hand in patients with hemiparesis, and to compare it with physical therapy rehabilitation.
DESIGN: Pretest-posttest design.
SETTING: Rehabilitation laboratory.
PARTICIPANTS: Volunteer sample of persons (N=12) with persistent hemiparesis from a single, unilateral stroke within the past 3 to 36 months.
INTERVENTIONS: The volunteers were randomly divided into 2 groups. One group was treated with a conventional program of physiotherapy, and another group participated in a training program in which an electromechanical orthosis was used. All volunteers received 24 sessions, held 3 times a week for 8 weeks.
MAIN OUTCOME MEASURES: Modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA), and electromyogram (EMG) amplitude.
RESULTS: No statistical difference was found in the initial and final values of the MAS. Both groups showed a significant increase for the total scores of the FMA. However, only the group treated with the orthosis showed an increase in FMA scores related to the wrist and hand joint. The EMG analysis showed increased EMG amplitudes for all muscles in the group treated with the orthosis, whereas the group treated with physiotherapy showed gains in electromyographic activity only in the extensor digitorum communis. Intergroup comparison showed that the initial FMA scores of the wrist/hand were higher in the group treated with physiotherapy. However, after training, the scores in the group that used the orthosis were equivalent to those of the physiotherapy group.
CONCLUSIONS: The results suggest that this device can be an auxiliary tool to help the conventional rehabilitation program of motor function of the affected upper extremity.

PMID: 21959035 [PubMed - indexed for MEDLINE]

Minimally invasive valve surgery with antegrade perfusion strategy is not associated with increased neurologic complications.

Ann Thorac Surg. 2011 Oct;92(4):1346-9; discussion 1349-50

Authors: Grossi EA, Loulmet DF, Schwartz CF, Solomon B, Dellis SL, Culliford AT, Zias E, Galloway AC

Abstract
BACKGROUND: A Society of Thoracic Surgeons' publication recently associated "minimally invasive" approaches with increased neurologic complications; this proposed association was questionable due to imprecise definitions. To critically reevaluate this issue, we reviewed a large minimally invasive valve experience with robust definitions.
METHODS: From November 1995 to January 2007, 3,180 isolated, non-reoperative valve operations were performed; 1,452 (45.7%) were aortic replacements and 1,728 (54.3%) were mitral valve procedures. Surgical approach was standard sternotomy (28%) or minimally invasive technique (72%). Antegrade arterial perfusion was used in 2,646 (83.2%) patients and retrograde perfusion in 534 (16.8%). Aortic clamping was direct in 83.4%, with endoclamp in 16.4% and no clamp in 0.2%. Patients were prospectively followed in a proprietary database and the New York State Cardiac Surgery Reporting System (mandatory, government audited). A neurologic event was defined as a permanent deficit, a transient deficit greater than 24 hours, or a new lesion on cerebral imaging.
RESULTS: Hospital mortality for aortic valve replacement was 4.0% (sternotomy [5.1%] versus minimally invasive [3.4%] p = 0.13); for mitral procedures it was 2.4% (sternotomy [4.8%] versus minimally invasive [1.8%] p = 0.001). Multivariate analysis revealed that age, female gender, renal disease, ejection fraction less than 0.30, chronic obstructive pulmonary disease, and emergent operation were risk factors for mortality. Stroke occurred in 71 patients (2.2%) (sternotomy [2.1%] versus minimally invasive [2.3%] p = 0.82). Multivariate analysis of neurologic events revealed that cerebrovascular disease, emergency procedure, no-clamp, and retrograde perfusion were risk factors. In patients 50 years old or younger (n = 662), retrograde perfusion had no significant impact on neurologic events (1.6% vs 1.1%, p = 0.57).
CONCLUSIONS: A minimally invasive approach with antegrade perfusion does not result in increased neurologic complications. Retrograde perfusion, however, is associated with increased neurologic risk in older patients.

PMID: 21958781 [PubMed - indexed for MEDLINE]

Presence of baseline prehypertension and risk of incident stroke: a meta-analysis.

Neurology. 2011 Oct 4;77(14):1330-7

Authors: Lee M, Saver JL, Chang B, Chang KH, Hao Q, Ovbiagele B

Abstract
OBJECTIVE: To qualitatively and quantitatively assess the association of prehypertension with incident stroke through a meta-analysis of prospective cohort studies.
METHODS: We searched Medline, Embase, the Cochrane Library, and bibliographies of retrieved articles. Prospective cohort studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95%confidence intervals (CI) of stroke with respect to baseline prehypertension.
RESULTS: Twelve studies with 518,520 participants were included. Prehypertension was associated with risk of stroke (RR 1.55, 95% CI 1.35-1.79; p < 0.001). Seven studies further distinguished a low prehypertensive population (systolic blood pressure [SBP] 120-129 mm Hg or diastolic blood pressure [DBP] 80-84 mm Hg) and a high prehypertensive population (SBP 130-139 mm Hg or DBP 85-89 mm Hg). Among persons with lower-range prehypertension, stroke risk was not significantly increased (RR 1.22, 0.95-1.57). However, for persons with higher values within the prehypertensive range, stroke risk was substantially increased (RR 1.79, 95% CI 1.49-2.16).
CONCLUSIONS: Prehypertension is associated with a higher risk of incident stroke. This risk is largely driven by higher values within the prehypertensive range and is especially relevant in nonelderly persons. Randomized trials to evaluate the efficacy of blood pressure reduction in persons with this designation are warranted.

PMID: 21956722 [PubMed - indexed for MEDLINE]

Interactions between nitrous oxide and tissue plasminogen activator in a rat model of thromboembolic stroke.

Anesthesiology. 2011 Nov;115(5):1044-53

Authors: Haelewyn B, David HN, Colloc'h N, Colomb DG, Risso JJ, Abraini JH

Abstract
BACKGROUND: Preclinical evidence in rodents has suggested that inert gases, such as xenon or nitrous oxide, may be promising neuroprotective agents for treating acute ischemic stroke. This has led to many thinking that clinical trials could be initiated in the near future. However, a recent study has shown that xenon interacts with tissue-type plasminogen activator (tPA), a well-recognized approved therapy of acute ischemic stroke. Although intraischemic xenon inhibits tPA-induced thrombolysis and subsequent reduction of brain damage, postischemic xenon virtually suppresses both ischemic brain damage and tPA-induced brain hemorrhages and disruption of the blood-brain barrier. The authors investigated whether nitrous oxide could also interact with tPA.
METHODS: The authors performed molecular modeling of nitrous oxide binding on tPA, characterized the concentration-dependent effects of nitrous oxide on tPA enzymatic and thrombolytic activity in vitro, and investigated the effects of intraischemic and postischemic nitrous oxide in a rat model of thromboembolic acute ischemic stroke.
RESULTS: The authors demonstrate nitrous oxide is a tPA inhibitor, intraischemic nitrous oxide dose-dependently inhibits tPA-induced thrombolysis and subsequent reduction of ischemic brain damage, and postischemic nitrous oxide reduces ischemic brain damage, but in contrast with xenon, it increases brain hemorrhages and disruption of the blood-brain barrier.
CONCLUSIONS: In contrast with previous studies using mechanical acute stroke models, these data obtained in a clinically relevant rat model of thromboembolic stroke indicate that nitrous oxide should not be considered a good candidate agent for treating acute ischemic stroke compared with xenon.

PMID: 21952256 [PubMed - indexed for MEDLINE]

Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke.

Neurology. 2011 Oct 4;77(14):1338-45

Authors: Finlayson O, Kapral M, Hall R, Asllani E, Selchen D, Saposnik G, ,

Abstract
OBJECTIVES: Pneumonia is the most common medical complication after stroke. Although several risk factors have been reported, the role of common comorbidities in the development of pneumonia is not well established. Moreover, there is discrepancy in the literature regarding the impact of pneumonia on stroke outcomes.
METHODS: This is a multicenter retrospective cohort study including consecutive patients with ischemic stroke admitted to Regional Stroke Centers participating in the Registry of Canadian Stroke Network in July 2003-March 2007. Pneumonia was defined as a complication that occurred within the first 30 days of the stroke and was confirmed radiographically. The main outcome measure was adjusted 30-day mortality. Secondary outcomes were adjusted 7- and 365-day mortality, institutionalization, length of stay, and modified Rankin score on discharge. We also assessed the impact of organized stroke care on pneumonia development and mortality.
RESULTS: Overall, 8,251 patients were included in the study. Stroke-associated pneumonia was observed in 587 patients (7.1%). Pneumonia increased 30-day (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.8-2.7]) and 1-year mortality (OR 3.0 [95% CI 2.5-3.7]), but not 7-day mortality. Pneumonia was associated with poor functional outcome. Higher access to organized inpatient care resulted in a reduction of 30-day mortality (OR 0.50 [95% CI 0.41-0.61]). Older age, male sex, stroke severity, dysphagia, chronic obstructive pulmonary disease, coronary artery disease, nonlacunar ischemic stroke, and preadmission dependency were independent predictors of pneumonia.
CONCLUSIONS: Development of pneumonia after stroke was associated with mortality at 30 days and 1 year, longer length of stay, and dependency at discharge. Patients who received more inpatient stroke services had reduced mortality after pneumonia.

PMID: 21940613 [PubMed - indexed for MEDLINE]